Molecular pharmacological aspects of antiarrhythmic activity, II: Interaction of class I compounds with calmodulin.
We have tested the calmodulin (CaM) inhibitory potency of class I antiarrhythmics in the phosphodiesterase (PDE) assay. The lipophilicity of the test compounds has been quantified by two experimental (log P, RM) and two calculative (sigma f, C log P) procedures. Five antiarrhythmics (asocainol, aprindine, lorcainide, propafenone, and ethmozine) exhibit IC50 values less than 250 microM for the inhibition of the CaM-stimulated PDE activity. Lipophilicity seems to be a prime, but not the sole descriptor of CaM inhibitory potency. The functional means of CaM inhibition by the test compounds for their antiarrhythmic properties remains to be clarified in further investigations.
Mannhold
R
R
Department of Clinical Physiology, Heinrich Heine Universität Düsseldorf, FRG.
Voigt
W
W
Bast
A
A
Timmerman
H
H
D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D010726:Phosphodiesterase Inhibitors
D000889:Anti-Arrhythmia Agents; D002147:Calmodulin; D010726:Phosphodiesterase Inhibitors